Navigation Links
Animal studies reveal new route to treating heart disease
Date:5/2/2011

Scientists at Johns Hopkins have shown in laboratory experiments in mice that blocking the action of a signaling protein deep inside the heart's muscle cells blunts the most serious ill effects of high blood pressure on the heart. These include heart muscle enlargement, scar tissue formation and loss of blood vessel growth.

Specifically, the Johns Hopkins team found that their intervention halted transforming growth factor beta (TGF-beta) secretion at a precise location called cell receptor type 2 in cardiac muscle cells. Blocking its action in this cell type forestalled pathways for hypertrophy, fibrosis, and angiogenesis by stopping the unbridled TGF-beta signaling, which is typically observed in heart failure, in all other non-muscle types of cells in blood vessels and fibrous tissue. However, blocking TGF-beta signaling in non-muscle cells did not stop disease progression.

In several dozen different experiments, using genetically altered mice or chemicals to selectively block different TGF-beta pathways, researchers were able to pinpoint where the signaling protein had its greatest impact on heart function and determine how its unimpeded activity promoted heart disease.

"Now that we know about the pivotal and specific bad roles played by TGF-beta in a common form of heart disease, we can try to mimic our lab experiments to develop cell-specific drug therapies that stop the chain reactions in the heart muscle at the TGF-beta type 2 cell receptor location," says senior study investigator and cardiologist, David Kass, M.D. Kass is a professor at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute.

The Kass team study, to be published in the June edition of the Journal of Clinical Investigation, is believed to show the first evidence of how TGF-beta is stimulated differently by various cell types in the heart and which resulting pathways promote heart failure, the most common kind of heart disease. Nearly 6 million Americans are estimated to have the condition.

Kass says previous research showed TGF-beta played a mixed role in various heart diseases, reducing arterial inflammation in some while harming valve and blood vessel function in others, such as people with Marfan syndrome. Until now, however, no explanation existed as to why any of these differences occurred, which cells controlled the TGF-beta signal, and which enzymes are stimulated as a result.

In the new study, researchers also found that in mice with hypertension-induced disease, blocking TGF-beta type 2 cell receptor stopped activities of another kind of regulating protein, called TGF-beta activated kinase (TAK-1). Its activation appears to play a key role in heart enlargement and in secreting proteins tied to scarring, as well as others tied to blood vessel formation.

Researchers began the study with injections of TGF-beta neutralizing antibodies to see if they could rein in heart-failing TGF-beta signaling. But the disease got worse in mice whose hearts had induced high blood pressure, and TGF-beta signaling persisted inside the muscle cells even though it was suppressed in other cells in the heart. The action of two other kinds of proteins closely tied to TGF-beta was similarly split, with the activity of Smad proteins suppressed only outside muscle cells, while TAK-1 production continued. This led Kass and his team to investigate what was happening differently inside muscle cells.

Subsequent testing in mice selectively bred to lack either one of the two TGF-beta receptors in the muscle cells revealed that blocking only the TGF-beta type 2 cell receptor shut down both Smad and TAK-1 activity, stalling enlargement and scarring. Blocking only the TGF-beta type 1 receptor, however, failed to block TAK-1 activity, and disease-accelerating TGF-beta signaling persisted in non-muscle heart cells.

Researchers plan further tests in animals of chemicals that block TAK-1 as potential treatments for heart failure or other kinds of heart disease.


'/>"/>

Contact: David March
dmarch1@jhmi.edu
410-955-1534
Johns Hopkins Medical Institutions
Source:Eurekalert

Related medicine news :

1. New clues found linking larger animals to colder climates
2. Ghrelin mitigates liver fibrosis in animal models; regulates human fibrosis
3. ATTENTION: Pawty Animals Needed in Nashville, Tennessee
4. Second Dose of Gene Therapy for Inherited Blindness Proves Safe in Animal Studies
5. Promega - TOP srl Agreement Enables Live Animal Imaging for Cancer Studies
6. Delray Beach and Boca Raton Veterinarian Launches New Web Sites for Atlantic Animal Hospital
7. Gunther von Hagens BODY WORLDS of Animals Opening March 19 at the Neunkirchen Zoo
8. Scout's House™ Announces Nation's First Animal Physical Rehabilitation Therapy Consultation Service for Veterinarians
9. 'Animals' Keep Germs Away From Kids' Toothbrushes
10. Science Reveals Secrets of Animals Spots, Stripes
11. The effect of dietary supplements, acids and animal protein on gastrointestinal disorders
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/6/2016)... (PRWEB) , ... May 06, 2016 , ... ... of a master charity program created to support and assist the people of ... days, working closely with nonprofit organizations and community leaders. Their desire is to ...
(Date:5/6/2016)... York (PRWEB) , ... May 06, 2016 , ... A wide variety of national pet ... Events Home, Garden and Safety Media Showcase Wednesday, May 18 from noon to 8 p.m. ... offers a sneak peek at new and established home, garden, outdoor and safety pet products ...
(Date:5/6/2016)... ... May 06, 2016 , ... Online HR/benefits platforms offer a range of benefits ... traditional brokers and health plans. “ The Rapid Emergence of Online Benefits Firms: Strategies ... Services, Inc. (AIS), will offer an accurate picture of online benefits today, and the ...
(Date:5/6/2016)... ... May 06, 2016 , ... Expert mattress researchers ... Since launching in September, 2014 Sleepopolis has resided at Sleepopolis-mattress-reviews.com . The ... pillows, sheets, mattress toppers, bed frames, and more. , Founder and Editor-in-Chief Derek ...
(Date:5/6/2016)... ... 2016 , ... This Mother’s Day kicks off the start of an important ... Women’s Health Week takes place May 8-May 14. , Throughout the celebration, the ... women to make their health a top priority. Women everywhere are being encouraged to ...
Breaking Medicine News(10 mins):
(Date:5/4/2016)... , May 4, 2016 According to ... Growth and Demand Forecast to 2022 - Industry Insights by ... Diagnostic Center and Others)" by P&S Market Research, the global ... in 2015, and it is expected to grow at a ... high slice type segment is expected to witness the faster ...
(Date:5/4/2016)... May 4, 2016 In ... a series of free workshops across ... requirements for Good Distribution Practices (GDP). Good ... ensures that products are consistently stored, transported and handled ... (MA) or product specification. Only a few years ago, ...
(Date:5/4/2016)... , May 4, 2016 ... of the  "Global Multiple Myeloma Market and ... their offering.       (Logo: ... Market and Competitive Landscape Highlights 2016, provides ... Multiple Myeloma epidemiology, Multiple Myeloma market valuations ...
Breaking Medicine Technology: